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Introduction
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Virtual Screening
 Virtual Ligand Screening
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 Ligand-Based
 Ride
  RIDE Setup
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13.4 RIDE Rapid Isostere Discovery Engine
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[ RIDE Setup ]

RIDE is a fast 3D molecular similarity search method based on Atomic Property Fields, developed at MolSoft. RIDE searches databases of compound conformers for molecules that are isosteric to the query, i.e. have similar 3D configurations and distributions of atomic properties.

GPU-based implementation is capable of searching ~0.5mln conformers/second on a single GPU card and perform 3D virtual screens of millions of compounds with the level of interactivity comparable to 2D searches. VLS benchmarking on DUDe indicates that RIDE searches produce enrichments on par with much slower standard flexible APF VLS.

RIDE applications include:

  • Virtual screening - efficiently screen "giga-sized" libraries.
  • Scaffold hopping - discover structurally novel chemicals based on a lead.
  • Hit follow-up - quickly discover new chemicals with similar 3D pharmacophoric binding properties to your lead.

A simple web-based interface is provided for the ease of use by chemists, or can be used in the ICM-Pro software. In either format, RIDE allows fine-tuning of the queries to generate most desirable hit lists. This includes:

  • Atom Weighting - Contributions of different portions of the molecule can be modulated with per-atom weights to reflect relative importance of certain moieties.
  • Excluded Volumes meet Shape Matching - An envelope penalty can be applied to the regions that surround all or part of the query molecule to prioritize hits without bulky extensions in constrained regions.

13.4.1 RIDE Setup


[ RIDE Server Setup ]

Prepare the template to search against:

  • Convert one or more chemicals to 3D.
  • If you are using more than one chemical in your template it the the chemicals need to be superimposed.

Download the pre-converted 3D database for screening:

Setup RIDE:

  • Chemistry/APF Tools/ Ride search...
  • Use the browse buttom to select the database you have downloaded that you wish to search against the template.
  • Select the 3D template - e.g. double click on it in the ICM Workspace.
  • Enter an APFcutoff. The APFCutoff [0-1] is the percentage of self score of the template. Lower the value - more hits are accepted.
  • You can choose to penalize the score if atoms are located outside the envelope. Select a repulsion weight and exclude margin. It penalize within + from template atoms. Note that if you have either envelope penalty or excluded volume you may need to lower the value.
  • You can choose to use an excluded volume to represent a pocket. In this case you would need to read in a PDB file and make sure your template molecules are superimposed in the pocket. Then check the excluded volume box and select the pdb structure using the drop down button.
  • "Refine maps": may give you better supposition because the final hits are realigned using maps with smaller step.

13.4.1.1 RIDE Server Setup


  • Chemistry/APF Tools/ Ride search...
  • Click on the Server tab

GPU-enabled RIDE server can be installed from Docker container (instructions are contained in download)

http://molsoft.com/distrib/docker/RIDE/

After the Docker is installed -paste the URL into URL box, press refresh button next to the database combo to refresh DB list.

Other parameters are the same as for local search (see above).


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